The Tat protein of HIV-1 human immunodeficiency virus 1 (HIV-1) plays an essential role in HIV gene expression by promoting efficient transcriptional elongation of viral transcripts. Tat binds to TAR, a conserved RNA stem-loop structure present in the nascent viral transcripts. Tat binding to TAR involves a highly conserved arginine-rich motif (ARM) in Tat and recruits the positive transcription elongation factor (pTEFb) to elongating HIV transcripts. Tat and the cyclinT1 component of pTEFb bind TAR RNA cooperatively and induce phosphorylation of the C-terminal domain of RNA polymerase II by the cyclinT1-associated kinase CDK9.
Tat is subject to several posttranslational modifications, including acetylation, ubiquitination and arginine methylation. The modification that is best studied in Tat is acetylation of lysine 50 (K50). This residue located in the Tat ARM is recognized by the HAT activities of p300 and human GCN5. Tat acetylation at K50 activates Tat function and coordinates the functions of Tat in polymerase phosphorylation and chromatin reorganization. Acetylated Tat cannot interact with cyclinT1 and TAR RNA but binds instead to the PCAF HAT via the PCAF bromodomain. Acetylated Tat also interacts with the Brg-1 subunit of the SWI/SNF chromatin-remodeling complex. It has also demonstrated that K50 acetylation is reversed by the nicotinamide adenine dinucleotide (NAD+)-dependent human sirtuin 1 (SIRT1).